Chemical methods and apparatus

Abstract

The invention relates to methods and apparatus for labelling a biologically active vector such as a peptide with reporter moiety such as a radionuclide. The methods comprise reaction of a compound of formula (I) with a compound of formula (II): R*-L2-N3 (II) or, a compound of formula (III) with a compound of formula (IV) wherein: L1, L2, L3, and L4 are each Linker groups; R* is a reporter moiety; in a narrow bore copper vessel. Microfluidic devices for performing the methods of the invention are also claimed.

1 . A method for labelling a vector comprising reaction of a compound of formula (I) with a compound of formula (II): 
     
       
         
         
             
             
         
       
       or, 
       a compound of formula (III) with a compound of formula (IV) 
     
     
       
         
         
             
             
         
       
       wherein: 
       L1, L2, L3, and L4 are each Linker groups; 
       R* is a reporter moiety; 
       to give a conjugate of formula (V) or (VI) respectively: 
     
     
       
         
         
             
             
         
       
       wherein L1, L2, L3, L4, and R* are as defined above; 
       characterised in that the reaction is performed in a narrow bore copper vessel. 
     
   
   
       2 . A method according to  claim 1  wherein R* comprises a radionuclide. 
   
   
       3 . A method according to  claim 1  wherein R* comprises a positron-emitting radionuclide, preferably  11 C or  18 F. 
   
   
       4 . A method according to  claim 1  wherein the vector is a peptide, protein, hormone, cell, bacterium, virus, or small drug-like molecule, most suitably a peptide. 
   
   
       5 . A method according to  claim 1  wherein the vector is Arg-Gly-Asp peptide or an analogue thereof. 
   
   
       6 . A method according to  claim 1  wherein the vector is a peptide comprising the fragment: 
     
       
         
         
             
             
         
       
     
   
   
       7 . A method according to  claim 1  wherein the vector is the peptide of formula (A): 
     
       
         
         
             
             
         
       
       wherein X 7  is either —NH 2  or 
     
     
       
         
         
             
             
         
       
       wherein a is an integer of from 1 to 10, preferably a is 1. 
     
   
   
       8 . Microfluidic device for performing a method according to  claim 1  characterised in that said device comprises a device body defining a first apperture, a second apperture, and at least one elongate microfluidic passageway in fluid communication therebetween wherein at least a portion of the microfluidic passageway is defined by a metallic copper portion of the device body. 
   
   
       9 . Microfluidic device according to  claim 8  wherein the device body defining the at least one microfluidic passageway is formed from metallic copper. 
   
   
       10 . Microfluidic device according to  claim 8  wherein the device body further comprises a base portion and a cover portion defining said first apperture, second apperture, and at least one elongate microfluidic passageway in fluid communication therebetween. 
   
   
       11 . Microfluidic device according to  claim 10  wherein the microfluidic passageway comprises a channel formed in either the base portion or the cover portion or in both thereof in overlying registry. 
   
   
       12 . Microfluidic device for performing a method according to  claim 1  characterised in that said device comprises a device body defining a first apperture, a second apperture, and at least one elongate microfluidic passageway in fluid communication therebetween wherein at least a portion of the microfluidic passageway is defined by a metallic copper portion of the device body wherein the microfluidic passageway contains a compound of formula (I), (II), (III), or (IV) as defined in any of  claim 1 .